MEP48608A - Piperazine containing phosphonic acid compounds as inhibitors of serine proteases - Google Patents

Piperazine containing phosphonic acid compounds as inhibitors of serine proteases

Info

Publication number
MEP48608A
MEP48608A MEP-486/08A MEP48608A MEP48608A ME P48608 A MEP48608 A ME P48608A ME P48608 A MEP48608 A ME P48608A ME P48608 A MEP48608 A ME P48608A
Authority
ME
Montenegro
Prior art keywords
phosphonic acid
acid compounds
inhibitors
serine proteases
containing phosphonic
Prior art date
Application number
MEP-486/08A
Other languages
Bosnian (bs)
English (en)
Inventor
Michael N Greco
Harold R Almond
Eugene Powell
Garavilla Lawrence De
Original Assignee
Ortho Mcneil Janssen Pharm
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ortho Mcneil Janssen Pharm filed Critical Ortho Mcneil Janssen Pharm
Publication of MEP48608A publication Critical patent/MEP48608A/xx

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3882—Arylalkanephosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/59—Hydrogenated pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
    • C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Ophthalmology & Optometry (AREA)
  • Virology (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
MEP-486/08A 2003-04-16 2004-04-14 Piperazine containing phosphonic acid compounds as inhibitors of serine proteases MEP48608A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/414,782 US7459461B2 (en) 2001-10-19 2003-04-16 Phosphonic acid compounds as inhibitors of serine proteases
PCT/US2004/011490 WO2004094441A2 (en) 2003-04-16 2004-04-14 Piperazine containing phosphonic acid compounds as inhibitors of serine proteases

Publications (1)

Publication Number Publication Date
MEP48608A true MEP48608A (en) 2011-02-10

Family

ID=33309497

Family Applications (1)

Application Number Title Priority Date Filing Date
MEP-486/08A MEP48608A (en) 2003-04-16 2004-04-14 Piperazine containing phosphonic acid compounds as inhibitors of serine proteases

Country Status (21)

Country Link
US (17) US7459461B2 (xx)
EP (1) EP1620446B1 (xx)
JP (1) JP4526534B2 (xx)
KR (1) KR101106574B1 (xx)
CN (1) CN100475824C (xx)
AU (1) AU2004232941B2 (xx)
BR (1) BRPI0409566A (xx)
CA (1) CA2523203C (xx)
CR (1) CR8046A (xx)
EA (1) EA200501463A1 (xx)
EC (1) ECSP056106A (xx)
ES (1) ES2399884T3 (xx)
HR (1) HRP20050899A2 (xx)
ME (1) MEP48608A (xx)
MX (1) MXPA05011218A (xx)
NO (1) NO20055396L (xx)
NZ (1) NZ543139A (xx)
RS (1) RS20050778A (xx)
UA (1) UA80869C2 (xx)
WO (1) WO2004094441A2 (xx)
ZA (1) ZA200509249B (xx)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7459461B2 (en) 2001-10-19 2008-12-02 Ortho-Mcneil Pharmaceutical, Inc. Phosphonic acid compounds as inhibitors of serine proteases
GB0224084D0 (en) 2002-10-16 2002-11-27 Glaxo Group Ltd Novel compounds
US20060293298A1 (en) * 2003-04-10 2006-12-28 Bamford Mark J Compounds
GB0308333D0 (en) * 2003-04-10 2003-05-14 Glaxo Group Ltd Novel compounds
KR101326537B1 (ko) * 2006-11-30 2013-11-08 (주)아모레퍼시픽 카텝신 ｇ 발현 억제제 조성물
EP2623599B1 (en) * 2007-10-04 2019-01-02 Roche Innovation Center Copenhagen A/S Micromirs
EP2058011A1 (en) * 2007-11-07 2009-05-13 Wittycell Nkt cell activating gycolipids covalently bound antigens and/or drug
JP5676480B2 (ja) 2009-12-25 2015-02-25 第一三共株式会社 ７員環化合物並びにその医薬用途
WO2016042131A1 (en) * 2014-09-18 2016-03-24 The Provost, Fellows, Foundation Scholars, & The Other Members Of Board, Of The College Of The Holy & Undiv. Trinity Of Queen Elizabeth Near Dublin Use of inhibitors of il-36 proteolytic processing for the treatment and/or reduction of inflammation

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE633914A (xx) 1962-06-22
US4511551A (en) * 1982-11-18 1985-04-16 Unique Technologies, Incorporated Method and composition for the detection of a precancerous or leukemic condition in mammals
AT380490B (de) * 1984-09-06 1986-05-26 Voest Alpine Ag Vorrichtung zur gewinnung der fuehlbaren waerme von schuettfaehigem heissgut
JPS61151199A (ja) * 1984-12-26 1986-07-09 Otsuka Pharmaceut Factory Inc カルボン酸アミド誘導体
US4704382A (en) 1985-07-29 1987-11-03 G. D. Searle & Co. Phenylpiperazine phosphonates
US4822780A (en) 1987-07-08 1989-04-18 Otsuka Pharmaceutical Factory, Inc. Carboxamide compounds
US5508273A (en) 1993-12-30 1996-04-16 Ortho Pharmaceutical Corporation Substituted phosphonic acids and derivatives useful in treating bone wasting diseases
EP0871454B1 (en) 1995-07-17 2003-11-12 Cephalon, Inc. Phosphorous-containing cysteine and serine protease inhibitors
EP0940400A4 (en) 1996-10-25 2002-10-02 Mitsubishi Pharma Corp NOVEL HETEROCYCLIC AMIDE COMPOUNDS AND THEIR USE FOR MEDICINAL PURPOSES
CN1550232A (zh) 1998-03-11 2004-12-01 杂环酰胺化合物在制备自身免疫性疾病抑制剂中的用途
CN100506831C (zh) 2001-10-19 2009-07-01 奥索-麦克尼尔药品公司 作为丝氨酸蛋白酶抑制剂的膦酸化合物
US7459461B2 (en) 2001-10-19 2008-12-02 Ortho-Mcneil Pharmaceutical, Inc. Phosphonic acid compounds as inhibitors of serine proteases
WO2007047431A2 (en) * 2005-10-12 2007-04-26 Kalypsys, Inc. Sulfonyl-substituted aryl compounds as modulators of peroxisome proliferator activated receptors

Also Published As

Publication number Publication date
US20090124581A1 (en) 2009-05-14
US20130281407A1 (en) 2013-10-24
UA80869C2 (en) 2007-11-12
JP4526534B2 (ja) 2010-08-18
US20090137528A1 (en) 2009-05-28
HRP20050899A2 (en) 2006-09-30
US8394804B2 (en) 2013-03-12
AU2004232941A1 (en) 2004-11-04
CR8046A (es) 2009-01-16
US20110086819A1 (en) 2011-04-14
US8207338B2 (en) 2012-06-26
RS20050778A (sr) 2008-04-04
EA200501463A1 (ru) 2006-08-25
NO20055396L (no) 2006-01-04
AU2004232941B2 (en) 2011-07-28
US20120238528A1 (en) 2012-09-20
US8212039B2 (en) 2012-07-03
ZA200509249B (en) 2007-01-31
CN100475824C (zh) 2009-04-08
US20090131671A1 (en) 2009-05-21
US20110092457A1 (en) 2011-04-21
US20090118504A1 (en) 2009-05-07
CA2523203C (en) 2013-06-11
KR101106574B1 (ko) 2012-01-19
US8497373B2 (en) 2013-07-30
EP1620446A2 (en) 2006-02-01
US20110319363A1 (en) 2011-12-29
WO2004094441A3 (en) 2005-10-13
US20040082544A1 (en) 2004-04-29
MXPA05011218A (es) 2006-07-06
US20090143336A1 (en) 2009-06-04
CA2523203A1 (en) 2004-11-04
US20090131371A1 (en) 2009-05-21
NO20055396D0 (no) 2005-11-15
US20120283221A1 (en) 2012-11-08
NZ543139A (en) 2009-02-28
WO2004094441A2 (en) 2004-11-04
US8461195B2 (en) 2013-06-11
US20090118508A1 (en) 2009-05-07
BRPI0409566A (pt) 2006-04-18
ECSP056106A (es) 2006-03-01
US8247599B2 (en) 2012-08-21
US8609888B2 (en) 2013-12-17
ES2399884T3 (es) 2013-04-04
CN1832950A (zh) 2006-09-13
US8304430B2 (en) 2012-11-06
US20090118234A1 (en) 2009-05-07
US8198440B2 (en) 2012-06-12
US7459461B2 (en) 2008-12-02
KR20060006929A (ko) 2006-01-20
US8178673B2 (en) 2012-05-15
JP2006523705A (ja) 2006-10-19
US20110092705A1 (en) 2011-04-21
US20090118235A1 (en) 2009-05-07
EP1620446B1 (en) 2012-10-24
US8703957B2 (en) 2014-04-22

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